Engineered 3D tumour model for study of glioblastoma aggressiveness and drug evaluation on a detachably assembled microfluidic device

Abstract3D models of tumours have emerged as an advanced technique in pharmacology and tumour cell biology, in particular for studying malignant tumours such as glioblastoma multiforme (GBM). Herein, we developed a 3D GBM model on a detachably assembled microfluidic device, which could be used to study GBM aggressiveness and for anti-GBM drug testing. Fundamental characteristics of the GBM microenvironment in terms of 3D tissue organisation, extracellular matrices and blood flow were reproduced in vitro by serial manipulations in the integrated microfluidic device, including GBM spheroid self-assembly, embedding in a collagen matrix, and continuous perfusion culture, respectively. We could realize multiple spheroids parallel manipulation, whilst, compartmentalized culture, in a highly flexible manner. This method facilitated investigations into the viability, proliferation, invasiveness and phenotype transition of GBM in a 3D microenvironment and under continuous stimulation by drugs. Anti-invasion effect of resveratrol, a naturally isolated polyphenol, was innovatively evaluated using this in vitro 3D GBM model. Temozolomide and the combination of resveratrol and temozolomide were also evaluated as control. This scalable model enables research into GBM in a more physiologically relevant microenvironment, which renders it promising for use in translational or personalised medicine to examine the impact of, or identify combinations of, therapeutic agents.